NOCICEPTION AND ROLE OF IMMUNE SYSTEM

Pain and inflammation, both are protective responses in living organisms. However, these self-limiting conditions (with established negative feedback loops) become pathological if left uncontrolled. This review explains nociception and inflammation briefly. This is followed by detailed description of role of immune and related cells in peripheral sensitization, phenomenon of neurogenic inflammation, and, alterations at sensory ganglia and CNS due to immune system during nociception. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards emotional elements associated with pain. However, there is a considerable role of immune system as analgesic and in resolution of pain. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

Introduction

One of the most vital functions of the nervous system is to provide information about the occurrence or threat of injury. On the other hand, Inflammation is a protective response involving host cells, blood vessels, and proteins and other mediators, which is intended to eliminate the initial cause of cell injury, as well as the necrotic cells and tissues resulting from the original insult, and to initiate the process of repair. A long-standing interest for pain scientists has been the identification of chemical mediators released into injured or diseased tissues that are responsible for the associated abnormal pain states. Moreover, it is well established that the immune system can alter the sensory processing and play pivotal role in the developmen...

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...longed acute pain.

A disproportion of pro-inflammatory and anti-inflammatory cytokines is known to be a contributory cause of pain and pain behavior. Embedded into psychoneuroendocrine and immunological feedback control systems, cytokines are able to perpetuate a vicious connection between local inflammation and systemic pain behavior (pain/sickness behavior), contributing towards chronification of nonspecific musculoskeletal pain. TNF-α (through NF-κB in astrocytes) causes release of CCL-2, which interacts positively with both NMDA and AMPA receptors in neurons. This adversely affects central descending pain modulation leading to failure of resolution state. Moreover; Co-localization of IL-1β and NMDA receptors on neuron, and, phosphorylation of NMDA on being stimulated by IL-1 explains direct role of immune system in establishing nociceptive neuronal circuit.